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Evaluation and Management of Dyslipidemia in Patients Treated with Lorlatinib
Normand Blais1, Jean-Philippe Adam2, John Nguyen2
1Service d'Hématologie-Oncologie, Département de Médicine, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC H2X 3E4, Canada.
Abstract:
The use of lorlatinib, an anaplastic lymphoma kinase (ALK) inhibitor for the treatment of ALK-positive metastatic non-small cell lung cancer, is associated with dyslipidemia in over 80% of patients. Clinical trial protocols for the management of lorlatinib-associated dyslipidemia differ from clinical practice guidelines for the management of dyslipidemia to prevent cardiovascular disease, in that they are based on total cholesterol and triglyceride levels rather than on the low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol levels that form the basis of current cardiovascular guideline recommendations. In order to simplify and harmonize the management of cardiovascular risk in patients with lorlatinib, an advisory committee consisting of a medical oncologist, a cardiologist, and two pharmacists with expertise in cardiology and oncology aimed to develop a simplified algorithm, adapted from the Canadian Cardiovascular Society dyslipidemia recommendations. Recommendations for the evaluation and management of hypercholesterolemia and isolated hypertriglyceridemia in patients treated with lorlatinib are outlined. These recommendations are based on data collected in a large number of lipid-lowering therapy trials applicable to individuals with and without cancer. Considering the relatively long life expectancy and improving prognosis of patients with ALK translocations, this specific patient population should be treated as are patients without cancer and are likely to derive the same benefits from lipid-lowering therapy.
Insights
Lorlatinib treatment for ALK-positive lung cancer causes dyslipidemia in most patients. A new algorithm simplifies managing lipid levels to reduce cardiovascular risk, aligning with current guidelines.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Lorlatinib, an ALK inhibitor for ALK-positive metastatic non-small cell lung cancer, is linked to dyslipidemia in over 80% of patients.
- Current clinical trial protocols for lorlatinib-associated dyslipidemia management differ from cardiovascular disease guidelines, focusing on total cholesterol and triglycerides instead of LDL-C and non-HDL-C.
Framework:
- An advisory committee developed a simplified algorithm for managing lorlatinib-induced dyslipidemia, adapted from Canadian Cardiovascular Society guidelines.
- The framework focuses on harmonizing cardiovascular risk management in patients receiving lorlatinib.
Implementation:
- Recommendations cover the evaluation and management of hypercholesterolemia and isolated hypertriglyceridemia in patients treated with lorlatinib.
- These recommendations are informed by extensive data from lipid-lowering therapy trials applicable to both cancer and non-cancer populations.
Implications:
- The simplified approach aims to align lorlatinib-associated dyslipidemia management with standard cardiovascular care.
- Patients with ALK translocations have improving prognoses and long life expectancies, warranting treatment similar to non-cancer patients for lipid management and cardiovascular risk reduction.
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